1. Field of the Invention
The present invention relates to a process for preparing an optically active tetrahydro-2-furoic acid, and, more particularly, to a process for preparing an optically active tetrahydro-2-furoic acid which comprises reacting (.+-.)-tetrahydro-2-furoic acid with a specific type of optically active amine resolver to produce an optically active diastereomer salt, followed by decomposition of the diastereomer salt.
2. Description of the Background Art:
In recent years, requirement for the use of optically active compounds for in the fields of pharmaceuticals, agrichemicals, foods, and the like is increasing. Conventionally, preparing optically active compounds involves difficulties in terms of production cost and manufacturing processes. Because of this, DL compounds have been used in many cases instead of optically active compounds. This, however, may bring about problems in case where one of the optical isomers is inactive or exhibits adverse side effects as in the case of thalidomide. For this reason, production of optically active pharmaceuticals is an important subject.
An optically active tetrahydro-2-furoic acid which is the subject of the present invention is expected to be used as an important pharmaceutical raw material as reported by P. C. Belanger et al. [Can. J. Chem. 61, 1383 (1983)]and by Japanese Patent Laid-open No. 207387/1986. One of the conventionally known processes for resolving optically active tetrahydro-2-furoic acids is that proposed by P. C. Belanger et al. This process involves the use of brucine dihydrate, which is an extremely expensive and highly toxic substance. In addition, its recovery rate is very low. Because of these reasons, great deal of improvement has to be done for the process to be industrially applied.
In this situation, for the purpose of developing a more practical process the present inventors have undertaken extensive studies, including investigations on the resolving agents, solvents, reaction conditions, methods of resolver recovery, and the like. As a result, the present inventors were successful in preparing the target optically active tetrahydro-2-furoic acid by reacting (.+-.)-tetrahydro-2-furoic acid with an optically active amine resolver having the formula (I) hereinafter given to produce an optically active diastereomer salt and by decomposing the diastereomer salt. The inventors have further developed a process in which the resolver could be recovered at a high yield and a high purity and a higher reaction concentration could be used. A mass-production of the optically active tetrahydro-2-furoic acid was also realized by the use of the process.